The sensitivity to capsaicin of substance P-immunoreactive nerve fibres in the hearts of guinea-pigs was examined. Capsaicin decreased considerably the substance P-immunoreactive material in nerve fibres of the parietal pericardium, atria, bicuspid and tricuspid valves. Pericardial and valvar nerve fibres localized by acetylcholinesterase (AChE) histochemistry had a distribution and density pattern similar to that of the substance P immunoreactive fibres. Capsaicin treatment also decreased the number of visible AChE-positive nerve fibres. It is known that capsaicin has a selective action on those substance P-immunoreactive fibres that are of sensory origin; thus, these results imply that substance P-immunoreactive fibres in the heart are sensory. Moreover, the results suggest that some of the nerve fibres localized in the heart by AChE histochemistry are substance P-containing sensory fibres.